A randomized phase II trial of trastuzumab plus capecitabine versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and taxanes: WJOG6110B/ELTOP. (August 2018)

• Record Type: Journal Article
• Authors: Takano, Toshimi; Tsurutani, Junji; Takahashi, Masato; Yamanaka, Takeharu; Sakai, Kazuko; Ito, Yoshinori; Fukuoka, Junya; Kimura, Hideharu; Kawabata, Hidetaka; Tamura, Kenji; Matsumoto, Koji; Aogi, Kenjiro; Sato, Kazuhiko; Nishio, Kazuto; Nakagawa, Kazuhiko; Saeki, Toshiaki
• Is Part Of: Breast. Volume 40(2018)
• Page Start: 67
• Page End: 75
• Publication Date: 2018-08
• Subjects: Lapatinib -- Trastuzumab -- Beyond progression -- PIK3CA -- Brain metastasis -- Circulating tumor DNA; Breast -- Diseases -- Periodicals; Breast -- Tumors -- Periodicals; Breast -- Periodicals; Electronic journals; Periodicals; 616
• DOI: 10.1016/j.breast.2018.04.010
• Languages: English
• ISSNs: 0960-9776

Abstract

Abstract: Background: For human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) with progression on trastuzumab-based therapy, continuing trastuzumab beyond progression and switching to lapatinib combined with chemotherapy are both valid options. We conducted an open-label, randomized phase II trial to compare the efficacy of these strategies. Patients and methods: Women with HER2-positive MBC previously treated with trastuzumab and taxanes were randomly assigned to receive trastuzumab plus capecitabine (HX) or lapatinib plus capecitabine (LX). The primary endpoint was progression-free survival (PFS) and the secondary endpoints included overall survival (OS) and the objective response rate (ORR). To explore the predictive value of the differential benefit of anti-HER2 drugs, PIK3CA mutations were assessed using circulating tumor DNA. Results: Eighty-six patients (43 in each arm) were enrolled. The median PFS was 6.1 months in the HX arm and 7.1 months in the LX arm (hazard ratio, 0.81; 90% CI, 0.55–1.21; p = 0.39); the median OS was 31.0 months in the HX arm and was not reached in the LX arm (hazard ratio, 0.58; 95% CI, 0.26–1.31; p = 0.18). The ORR was 40% in the HX arm and 41% in the LX arm. PIK3CA mutations were detected in 23% of the 35 analyzed patients, and in patients without PIK3CA mutations, LX yielded relatively longer PFS and OS than HX. Conclusion: In women with HER2-positive MBC previously treated with trastuzumab and taxanes, no significant differences in PFS and OS were observed between patients treated with LX and HX. Trial registration number: UMIN000005219. Highlights: This is a randomized phase II trial in HER2-positive metastatic breast cancer. We compared trastuzumab beyond progression and switching to lapatinib. No significant differences in PFS and OS were observed between the two groups. Lapatinib may be more effective in patients without PIK3CA mutations. Efficacy on brain metastasis was similar between lapatinib and trastuzumab.